Stress-activated MAPK signalling controls fission yeast actomyosin ring integrity by modulating formin For3 levels

  1. Elisa Gómez-Gil
  2. Rebeca Martín-García
  3. Jero Vicente-Soler
  4. Alejandro Franco
  5. Beatriz Vázquez-Marín
  6. Francisco Prieto-Ruiz
  7. Teresa Soto
  8. Pilar Pérez
  9. Marisa Madrid  Is a corresponding author
  10. Jose Cansado  Is a corresponding author
  1. Universidad de Murcia, Spain
  2. Instituto de Biología Funcional y Genómica/Universidad de Salamanca, Spain

Abstract

Cytokinesis, which enables the physical separation of daughter cells once mitosis has been completed, is executed in fungal and animal cells by a contractile actin- and myosin-based ring (CAR). In the fission yeast Schizosaccharomyces pombe the formin For3 nucleates actin cables and also co-operates for CAR assembly during cytokinesis. Mitogen-Activated Protein Kinases (MAPKs) regulate essential adaptive responses in eukaryotic organisms to environmental changes. We show that the Stress Activated Protein Kinase pathway (SAPK) and its effector, MAPK Sty1, downregulates CAR assembly in S. pombe when its integrity becomes compromised during cytoskeletal damage and stress by reducing For3 levels. Accurate control of For3 levels by the SAPK pathway may thus represent a novel regulatory mechanism of cytokinesis outcome in response to environmental cues. Conversely, SAPK signalling favours CAR assembly and integrity in its close relative S. japonicus, revealing a remarkable evolutionary divergence of this response within the fission yeast clade.

Data availability

All data generated or analysed during this study are included within the manuscript and supporting files.

Article and author information

Author details

  1. Elisa Gómez-Gil

    Genetics and Microbiology, Universidad de Murcia, Murcia, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Rebeca Martín-García

    Morfogénesis y Polaridad Celular, Instituto de Biología Funcional y Genómica/Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Jero Vicente-Soler

    Genetics and Microbiology, Universidad de Murcia, Murcia, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Alejandro Franco

    Genetics and Microbiology, Universidad de Murcia, Murcia, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Beatriz Vázquez-Marín

    Genetics and Microbiology, Universidad de Murcia, Murcia, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Francisco Prieto-Ruiz

    Genetics and Microbiology, Universidad de Murcia, Murcia, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Teresa Soto

    Genetics and Microbiology, Universidad de Murcia, Murcia, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2965-318X
  8. Pilar Pérez

    Morfogénesis y Polaridad Celular, Instituto de Biología Funcional y Genómica/Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Marisa Madrid

    Genetics and Microbiology, Universidad de Murcia, Murcia, Spain
    For correspondence
    marisa@um.es
    Competing interests
    The authors declare that no competing interests exist.
  10. Jose Cansado

    Genetics and Microbiology, Universidad de Murcia, Murcia, Spain
    For correspondence
    jcansado@um.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2342-8152

Funding

Ministerio de Economía y Competitividad (BFU2017-82423-P)

  • Jose Cansado

Ministerio de Economía y Competitividad (PGC2018-098924-B-100)

  • Pilar Pérez

Junta de Castilla y Leon (CLU-2017-03)

  • Pilar Pérez

Fundacion Seneca (20856/PI/18)

  • Jose Cansado

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2020, Gómez-Gil et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,868
    views
  • 282
    downloads
  • 17
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Elisa Gómez-Gil
  2. Rebeca Martín-García
  3. Jero Vicente-Soler
  4. Alejandro Franco
  5. Beatriz Vázquez-Marín
  6. Francisco Prieto-Ruiz
  7. Teresa Soto
  8. Pilar Pérez
  9. Marisa Madrid
  10. Jose Cansado
(2020)
Stress-activated MAPK signalling controls fission yeast actomyosin ring integrity by modulating formin For3 levels
eLife 9:e57951.
https://doi.org/10.7554/eLife.57951

Share this article

https://doi.org/10.7554/eLife.57951

Further reading

    1. Cell Biology
    Dan Wu, Venkateswararao Eeda ... Weidong Wang
    Research Article

    Overnutrition engenders the expansion of adipose tissue and the accumulation of immune cells, in particular, macrophages, in the adipose tissue, leading to chronic low-grade inflammation and insulin resistance. In obesity, several proinflammatory subpopulations of adipose tissue macrophages (ATMs) identified hitherto include the conventional ‘M1-like’ CD11C-expressing ATM and the newly discovered metabolically activated CD9-expressing ATM; however, the relationship among ATM subpopulations is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) is activated in the adipocytes and immune cells under obesity. It is unknown whether targeting IRE1α is capable of reversing insulin resistance and obesity and modulating the metabolically activated ATMs. We report that pharmacological inhibition of IRE1α RNase significantly ameliorates insulin resistance and glucose intolerance in male mice with diet-induced obesity. IRE1α inhibition also increases thermogenesis and energy expenditure, and hence protects against high fat diet-induced obesity. Our study shows that the ‘M1-like’ CD11c+ ATMs are largely overlapping with but yet non-identical to CD9+ ATMs in obese white adipose tissue. Notably, IRE1α inhibition diminishes the accumulation of obesity-induced metabolically activated ATMs and ‘M1-like’ ATMs, resulting in the curtailment of adipose inflammation and ensuing reactivation of thermogenesis, without augmentation of the alternatively activated M2 macrophage population. Our findings suggest the potential of targeting IRE1α for the therapeutic treatment of insulin resistance and obesity.

    1. Cell Biology
    Dharmendra Kumar Nath, Subash Dhakal, Youngseok Lee
    Research Advance

    Understanding how the brain controls nutrient storage is pivotal. Transient receptor potential (TRP) channels are conserved from insects to humans. They serve in detecting environmental shifts and in acting as internal sensors. Previously, we demonstrated the role of TRPγ in nutrient-sensing behavior (Dhakal et al., 2022). Here, we found that a TRPγ mutant exhibited in Drosophila melanogaster is required for maintaining normal lipid and protein levels. In animals, lipogenesis and lipolysis control lipid levels in response to food availability. Lipids are mostly stored as triacylglycerol in the fat bodies (FBs) of D. melanogaster. Interestingly, trpγ deficient mutants exhibited elevated TAG levels and our genetic data indicated that Dh44 neurons are indispensable for normal lipid storage but not protein storage. The trpγ mutants also exhibited reduced starvation resistance, which was attributed to insufficient lipolysis in the FBs. This could be mitigated by administering lipase or metformin orally, indicating a potential treatment pathway. Gene expression analysis indicated that trpγ knockout downregulated brummer, a key lipolytic gene, resulting in chronic lipolytic deficits in the gut and other fat tissues. The study also highlighted the role of specific proteins, including neuropeptide DH44 and its receptor DH44R2 in lipid regulation. Our findings provide insight into the broader question of how the brain and gut regulate nutrient storage.